ABSTRACT The overall goal of this research is to identify efficacious strategies for treating tobacco dependence among adult smokers hospitalized with severe mental illness. Nicotine dependence is the most prevalent substance abuse disorder among psychiatric patients, a group that accounts for a staggering 44% to 46% of the US tobacco market16, 17. In terms of dollars spent, this equates to $39 billion in annual tobacco sales18. While numerous trials have established the effectiveness of smoking cessation interventions for hospitalized medical patients, little research has targeted the acute psychiatric inpatient setting19. The American Psychiatric Association's tobacco treatment guidelines identify psychiatric hospitalization as an ideal opportunity for promoting smoking cessation1. Individuals with mental illness have lower quit rates and may be less motivated and prepared to quit in the near future than the general population20-22. Thus, sufficiently intense, multi- component interventions are needed that address both the physiological and behavioral aspects of nicotine dependence and assist smokers at all stages of readiness through the quitting process23. Using a three group additive design, the proposed randomized clinical trial (N=1100) aims to evaluate tobacco cessation treatments of varying intensities initiated in the acute psychiatric inpatient setting. The proposal builds upon Dr. Prochaska's K23 mentored career development award and seeks to determine: (i) whether the initial successes seen in an academic-based psychiatric hospital can be replicated in a larger and more diverse patient population recruited from a community hospital; and (ii) if more extended and intensive clinician-delivered treatment can outperform our current best practices. The three groups are: (1) Usual Care (N=150) consisting of brief cessation advice, a quit smoking guide, and nicotine replacement provided during hospitalization; (2) Brief Treatment (N=475) adds a stage-based manual, computer-delivered stage-tailored individualized feedback and brief cessation counseling sessions during hospitalization and repeated at months 3 and 6, and access to 12 weeks of nicotine replacement following hospitalization; (3) Extended Treatment (N=475) builds upon our current brief treatment and provides 12 additional weeks of nicotine replacement (24 weeks total) with individualized, counselor-delivered motivational and manualized cognitive behavioral cessation treatment. We hypothesize that the extended treatment will outperform the brief treatment, and that both treatment groups will be more effective than usual care in producing quit attempts and ultimately abstinence from cigarettes. Secondary aims will model the cost-effectiveness of the treatment conditions; examine moderators and mediators of treatment outcomes; and prospectively examine the relation between changes in smoking, mental health functioning, and use of other substances over time.